The enzyme NADPH oxidase transfers electrons from NADPH to oxygen, resulting in the generation of reactive oxygen species (ROSs), including O2− and H2O2. NADPH oxidase is expressed in neutrophils where bursts of reactive oxygen species are utilized to kill pathogens. NADPH oxidase expression and activity is also observed in other cells and tissues of the mammalian body, in which it functions as a modulator of intracellular signaling pathways.
Unfortunately, in a high proportion of non-infectious pathologies, NADPH oxidase becomes overexpressed and/or overactivated in affected tissues, and the resulting production of oxidants often either mediates or exacerbates the pathology. Indeed, activated NADPH oxidase appears to be the chief source of excess oxidant stress in most pathological disorders. NADPH oxidase overactivity can stimulate pro-inflammatory mechanisms, promote tissue fibrosis and bone resorption, and, in the vascular system, antagonize the crucial protective activity of nitric oxide. Oxidants produced by NADPH oxidase can also induce structural damage to critical cellular targets, including DNA, and can boost the growth factor activity of cancers. (Meyer J W et al. FEBS Lett 2000; 472:1-4; Zalba G et al. Hypertension 2001; 38:1395-9; Inoguchi T et al. J Am Soc Nephrology 2003; 14:S227-32; Li J M et al. Hypertension 2002; 40:477-84; Bateller R et al. J Clin Invest 2003:112:1383-94; Darden A G et al. J Bone Mineral Res 1996; 11:671-5; Ohshima H et al. Arch Biochem Biophys 2003; 417:3-11; Mander P et al. J Neuroinflammation 2005; 2:20; Brar S S et al. Am J Physiol Cell Physiol 2002; 282:C1212-24; and other citations below.) Thus, there is a widespread consensus among medical scientists that safe strategies for achieving partial inhibition of NADPH oxidase activity could have considerable utility for prevention and/or treatment of a wide range of disorders.
Indeed, it is now believed that the beneficial effects of certain commonly used drugs, including statins and ACE inhibitors, are mediated in part by an indirect suppression of NADPH oxidase activity in certain tissues. However, to date no drug or phytonutrient is currently available for clinical or dietary use that can directly inhibit NADPH oxidase activity in most or all tissues.
Hence, what is needed is an inhibitor of NADPH oxidase that can be readily mass produced, that can be used to inhibit NADPH oxidase activity, and that can be used to prevent or treat conditions associated with NADPH oxidase activity.